Funds are requested to purchase a Thermo Fisher LTQ Orbitrap XL mass spectrometer, a micro HPLC system and computer cluster hardware for the Institutional Mass Spectrometry Laboratory of the University of Texas Health Science Center at San Antonio, under the direction of Dr. Susan Weintraub, who has over 30 years experience in biomedical mass spectrometry. At the present time, capillary HPLC-ESIMS/ MS analyses are conducted on a heavily-utilized Thermo Fisher LTQ that was installed in October 2005. There are no high resolution/high mass accuracy mass spectrometers in San Antonio. The major uses for the requested instrument will be for assessing relative differences in protein quantities and for identifying sites of protein modification. The projects of nine major users and two future users are presented. Medically-relevant areas that will be studied by the major users include cardiovascular disease, diabetes, ethanol exposure and maternal/fetal nutrition;in addition, a wide variety of key biochemical systems will be investigated, such as bacteriophage assembly, cell contact-mediated processes, metabolic defects due to loss of individual TCA cycle enzymes, NADPH-cytochrome P450 oxidoreductase, nitric oxide synthase and modification of mitochondrial electron transport complexes. The requested Orbitrap XL will enhance the projects of the user group in many ways. The acquisition of high mass accuracy precursor ion spectra will substantially lower false discovery rates, leading to higher confidence for protein identifications. High mass resolution will be essential for charge state determinations and for differentiating between nearly isobaric species. The availability of multiple fragmentation strategies (CAD, HCD and ETD) will result in more successful localization of sites of modification and greater sequence coverage for protein identification/characterization. Finally, the capability of top-down analysis in conjunction with ETD will facilitate comprehensive characterization of large peptides and small proteins. In addition to the proposed user group, availability of the Orbitrap will stimulate other investigators to plan new experiments in the future that may take their research endeavors into exciting new directions. Thus, acquisition of the Orbitrap has the potential to positively impact a large number of NIH-funded investigations covering the full array of disciplines in biomedical research. PUBLIC HEALTH RELEVANCE Acquisition of the requested Orbitrap XL mass spectrometer will advance the research efforts of nine major users in six different departments at the University of Texas Health Science Center at San Antonio. Medically-relevant areas that will be studied by the major users include cardiovascular disease, diabetes, ethanol exposure and maternal/fetal nutrition;in addition, a wide variety of key biochemical systems will be investigated. Beyond the proposed user group, availability of the Orbitrap will stimulate other investigators to plan new experiments in the future that may take their biomedical research endeavors into exciting new directions.